Category: Technical References, EpiDerm
203. IL-1-RELATED CYTOKINE RESPONSES OF NONIMMUNE SKIN CELLS SUBJECTED TO CEES EXPOSURE WITH AND WITHOUT POTENTIAL VESICANT ANTAGONISTS.
Blaha1, M., Bowers, Jr.1, W., Kohl1, J., DuBose1, D., Walker2, J. 1U.S. Army Research Institute of Environmental Medicine. 2U.S. Army Soldier and Biological Chemical Command, Natick, MA 01760. In Vitro & Molecular Toxicology, 13, (2), 99, (2000).
Summary: Sulfur mustard provokes an acute inflammatory response in skin. To determine if keratinocytes regulate this response and whether three potential vesicant antagonists can counteract adverse changes, specimens of EpiDerm™ (MatTek Corp., Ashland, MA), a human skin model of differentiating keratinocytes, were exposed 2 h to humidified air with or without 2-chloroethyl ethyl sulfide (CEES. 1.72-4.73 mg/L/min) with or without 10 mM niacinamide, a poly (ADP-ribose) polymerase (PARP) inhibitor, 25 uM CG59343B (calmodulin antagonist), or 8.4 mM leupeptin (cysteine protease inhibitor). After a 22 h incubation, levels of interleukin-1 alpha (IL-1α), its receptor antagonist (IL-1Ra), soluble type II receptor (sIL-1RII) and prostaglandin-E2 (PGE-2) were determined. Methylthiazole tetrazolium (MTT) viability tests and histological observations were also conducted. PGE-2 levels were abundant but unaffected by CEES regardless of antagonist pres-ence. Total amounts (media plus lysate) of IL-1α, IL-1Ra, and sIL-1RII were reduced with CEES irrespective of antagonist. CEES promoted the release of IL-1Ra. Exposure of EpiDerm to CEES in the presence of the vesicant antagonists did not improve viability or counteract histological damage. We conclude CEES de-presses total IL-1α and related cytokines, does not affect PGE-2 release, and adverse changes associated with CEES-exposed EpiDerm are not ameliorated by these particular antagonists. Dramatically increased (5- to 10-fold) release of IL-1Ra may provide a useful marker for cytotoxicity. The high level of IL-1Ra and increased release with injury suggest a primary function in down-regulating IL-1 inflammatory responses in skin.
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EpiDerm Data Sheet
EpiDerm Technical References
Applications: Cytokine expression/analysis, General research - skin, Inflammation - skin
Keywords: Antagonists, Cees exposure, Cytokines, EpiDerm, IL-1, IL-1a, Inflammation, Inflammatory, Inflammatory response, Non-immune skin cells